Antibiotic eluting poly(ester urea) films, meshes and pouches for infection control of implantable medical devices

Abstract

In various embodiments, the present invention is directed to a drug-loaded amino acid based poly(ester urea) pouch or pocket sized to receive implanted devices that produces localized drug delivery. In some embodiments, the present invention is directed to an antibiotic-loaded L-Valine poly(ester urea) pouch or pocket that provides localized antibiotic delivery for CIEDs or other implanted devices. In one or more embodiments, the amount and rate of antibiotic release are dependent upon the thickness and loading concentration of the film. This dependence of release on thickness and loading concentration gives a handle to fabricate PEU-A pouches or pockets with any desired release profile that can locally deliver the therapeutically relevant amount of antibiotic.

What is claimed is: 
     
         1 . A pouch for implantation in the body, wherein said pouch has a shape for encasing a medical device and comprises a drug loaded amino acid-based poly(ester urea) polymer or copolymer. 
     
     
         2 . The pouch of  claim 1  wherein said medical device is selected from the group consisting of cardiac implantable electronic devices (CIEDs), pace makers, implantable cardioverter defibrillators (ICDs), artificial heart valves, surgical mesh, hernia mesh films, transvaginal mesh, transabdominal mesh, sutures, shunts, stents, adhesion barriers, tissue scaffolds, auditory implants, ear tubes, cochlear implants, neurological implants, neural implants, implantable gastric stimulators, diaphragmatic/phrenic nerve stimulators, orthopedic implants, joint replacement appliances, spinal fusion hardware, surgical hardware for fracture repair (metal plates, pins, screws, rods, etc.), contraceptive implants, intra-uterine devices (IUDs), or cosmetic implants, implantable prostheses, and combinations thereof. 
     
     
         3 . The pouch of  claim 1  wherein said drug loaded amino acid-based poly(ester urea) polymer or copolymer comprises a therapeutically effective amount of a drug selected from the group consisting of antibiotics, cancer drugs, antipsychotics, antidepressants, sleep aids, tranquillizers, anti-Parkinson's drugs, mood stabilizers, pain killers, anti-inflammatories, anti-microbials, and combinations and pharmaceutically acceptable salts thereof. 
     
     
         4 . The pouch of  claim 1  wherein said drug loaded amino acid-based poly(ester urea) polymer or copolymer comprises a therapeutically effective amount of an antibiotic or pharmaceutically acceptable salt thereof. 
     
     
         5 . The pouch of  claim 1  wherein said drug loaded amino acid-based poly(ester urea) polymer comprises a therapeutically effective amount of an antimicrobial or pharmaceutically acceptable salt thereof. 
     
     
         6 . The pouch of  claim 1  wherein drug loaded amino acid-based poly(ester urea) polymer or copolymer comprises residues of two or more amino acid based diester monomer segments joined by urea linkages. 
     
     
         7 . The pouch of  claim 6  wherein the two or more amino acid based diester monomer segments have the formula: 
       
         
           
           
               
               
           
         
         wherein R is —CH 3 , —(CH 2 ) 3 NHC(NH 2 )C═NH, —CH 2 CONH 2 , —CH 2 COOH, —CH 2 SH, —(CH 2 ) 2 COOH, —(CH 2 ) 2 CONH 2 , —NH 2 , —CH 2 C═CH—N═CH—NH, —CH(CH 3 ) CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —(CH 2 ) 4 NH 2 , —(CH 2 ) 2 SCH 3 , —CH 2 Ph, —CH 2 OH, —CH(OH)CH 3 , —CH 2 —C═CH—NH-Ph, —CH 2 -Ph-OH, —CH(CH 3 ) 2 , or —CH 2 C 6 H 4 OCH 2 C 6 H 5  and a is an integer from 1 to 20. 
       
     
     
         8 . The pouch of  claim 6  wherein said drug loaded amino acid-based poly(ester urea) polymer or copolymer comprises a copolymer containing two or more different types of amino acid based diester monomer segments joined by urea linkages. 
     
     
         9 . The resorbable pouch of  claim 8  wherein said copolymer has the formula: 
       
         
           
           
               
               
           
         
         where a and a′ are each an integer from about 1 to about 20; m and n are mole fractions greater than 0; each R and R′ are amino acid side groups or functionalized amino acid side groups 
       
     
     
         10 . The pouch of  claim 1  wherein said pouch encases at least 50% of the volume of said medical device. 
     
     
         11 . The pouch of  claim 1  wherein said pouch is sufficiently porous to permit said medical device to be electrically grounded to surrounding tissue. 
     
     
         12 . A resorbable pouch sized to at least partially enclose an implantable medical device comprising a drug loaded amino acid-based poly(ester urea) polymer or copolymer. 
     
     
         13 . The resorbable pouch of  claim 12  wherein the implantable medical device is selected from the group consisting of cardiac implantable electronic devices (CIEDs), pace makers, implantable cardioverter defibrillators (ICDs), artificial heart valves, surgical mesh, hernia mesh films, transvaginal mesh, transabdominal mesh, sutures, shunts, stents, adhesion barriers, tissue scaffolds, auditory implants, ear tubes, cochlear implants, neurological implants, neural implants, implantable gastric stimulators, diaphragmatic/phrenic nerve stimulators, orthopedic implants, joint replacement appliances, spinal fusion hardware, surgical hardware for fracture repair (metal plates, pins, screws, rods, etc.), contraceptive implants, intra-uterine devices (IUDs), or cosmetic implants, implantable prostheses, and combinations thereof. 
     
     
         14 . The resorbable pouch of  claim 12  wherein said drug loaded amino acid-based poly(ester urea) polymer or copolymer comprises an amino acid-based poly(ester urea) polymer or copolymer and a drug wherein said drug is substantially evenly distributed throughout said amino acid-based poly(ester urea) polymer. 
     
     
         15 . The resorbable pouch of  claim 12  wherein said drug loaded amino acid-based poly(ester urea) polymer or copolymer comprises a polymer having the formula: 
       
         
           
           
               
               
           
         
         wherein R is —CH 3 , —(CH 2 ) 3 NHC(NH 2 )C═NH, —CH 2 CONH 2 , —CH 2 COOH, —CH 2 SH, —(CH 2 ) 2 COOH, —(CH 2 ) 2 CONH 2 , —NH 2 , —CH 2 C═CH—N═CH—NH, —CH(CH 3 ) CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —(CH 2 ) 4 NH 2 , —(CH 2 ) 2 SCH 3 , —CH 2 Ph, —CH 2 OH, —CH(OH)CH 3 , —CH 2 —C═CH—NH-Ph, —CH 2 -Ph-OH, —CH(CH 3 ) 2 , or —CH 2 C 6 H 4 OCH 2 C 6 H 5  and a is an integer from 1 to 20. 
       
     
     
         16 . The resorbable pouch of  claim 12  wherein said drug loaded amino acid-based poly(ester urea) polymer or copolymer comprises a copolymer having the formula: 
       
         
           
           
               
               
           
         
         where a and a′ are each an integer from about 1 to about 20; m and n are mole fractions greater than 0; each R and R′ are amino acid side groups or functionalized amino acid side groups 
       
     
     
         17 . The resorbable pouch of  claim 12  wherein said drug loaded amino acid-based poly(ester urea) polymer comprises a therapeutically effective amount of a drug selected from the group consisting of antibiotics, cancer drugs, antipsychotics, antidepressants, sleep aids, tranquillizers, anti-Parkinson's drugs, mood stabilizers, pain killers, anti-inflammatories, anti-microbials, and combinations thereof. 
     
     
         18 . The resorbable pouch of  claim 12  wherein said drug loaded amino acid-based poly(ester urea) polymer comprises a therapeutically effective amount of an antibiotic compound. 
     
     
         19 . The resorbable pouch of  claim 12  wherein said drug loaded amino acid-based poly(ester urea) polymer comprises a therapeutically effective amount of an antimicrobial compound. 
     
     
         20 . A method for retarding biofilm formation on an implantable medical device comprising:
 (a) enveloping or covering an implantable medical device, in whole or in part, in a polymer pouch comprising a drug loaded amino acid-based poly(ester urea) polymer or copolymer comprising one or more antibacterial or antimicrobial agents; and   (b) implanting the enveloped or covered implantable medical device into the body of a subject;   wherein said one or more antibacterial or antimicrobial agents are released into the body of the subject and act to retard biofilm formation.   
     
     
         21 . The method of  claim 20  wherein the implantable medical device is at least 50% enveloped or covered by said polymer pouch. 
     
     
         22 . The method of  claim 20  wherein all external surfaces of the implantable medical device are enveloped or covered by said polymer pouch. 
     
     
         23 . The method of  claim 20  wherein said one or more antibacterial or antimicrobial agents is an antibiotic agent selected from the group consisting of lipopeptides, fluoroquinolone, lipoglycopeptides, cephalosporins, penicillins, monobactams, carbapenems, macrolide antibiotics, lincosamides, streptogramins, aminoglycoside antibiotics, quinolone antibiotics, sulfonamides, tetracycline antibiotics, chloraphenicol, metronidazole, tinidazole, nitrofurantoin, glycopeptides, oxazolidinones, rifamycins, polypeptides, tuberactinomycins, and combinations and pharmaceutically acceptable salts thereof. 
     
     
         24 . The method of  claim 20  wherein said polymer pouch is the pouch for implantation in the body of  claim 1 . 
     
     
         25 . The method of  claim 20  wherein said polymer pouch is the resorbable pouch of  claim 12 .